聚肌苷酸胞苷酸增强间充质干细胞对脓毒症大鼠肠屏障功能的保护作用

Poly( I: C)-pretreated MSCs protect intestinal barrier function in rats after sepsis

目的观察间充质干细胞(mesenchymal stem cells,MSCs)及聚肌苷酸胞苷酸poly(I:C)预刺激MSCs对脓毒症大鼠肠屏障功能的保护作用。方法采用盲肠结扎穿孔(cecal ligation puncture,CLP)诱导大鼠脓毒症模型,将SD大鼠随机分为5个组:正常对照组、脓毒症组、常规治疗组(乳酸林格液体复苏+血管活性药多巴胺+头孢呋辛钠)、MSCs治疗组(MSCs 3×106/只+常规治疗)和ploy(I:C)预刺激MSCs组[poly(I:C)20μg/m L预刺激MSCs 24 h+常规治疗],观察不同处理组大鼠肠通透性,血中D乳酸、细菌内毒素浓度、肠病理组织形态及动物存活时间、存活率的变化。结果与正常对照组相比,脓毒症大鼠肠通透性、血中D乳酸、细菌内毒素浓度显著增高(P<0.01),病理结果显示肠绒毛断裂、减少,上皮细胞坏死脱落,炎细胞、红细胞增多。常规治疗后第3天,同脓毒症组相比,大鼠肠通透性有改善,血D乳酸、细菌内毒素含量降低,肠绒毛损害及炎症减轻,长度增加;MSCs+常规治疗后效果明显优于常规治疗组,而poly(I:C)预刺激MSC可增强MSCs对肠屏障功能的保护作用,肠通透性及血中D乳酸、内毒素浓度显著降低(P<0.05),病理结果显示肠上皮增生修复,肠绒毛增多,炎症明显减轻。结论 poly(I:C)可增强MSC对脓毒症大鼠肠屏障功能的保护作用。

Objective To determine the protective effects of mesenchymal stem cells（ MSCs） and polyriboinosinic： polyribocytidylic acid [poly（ I： C） ] pre-stimulated MSCs on the intestinal barrier function in sepsis rats. Methods The sepsis model of rats was established with cecal ligation and puncture（ CLP）. SD rats were randomly divided into normal control, sepsis, conventional treatment（ conventional fluid resuscitation ＋ dopamine ＋ cefuroxime,CT）,MSCs ＋ CT（ MSCs 3 × 106 cells / animal） and ploy（ I： C） prestimulated MSCs ＋ CT groups [MSC was pre-stimulated by poly（ I： C） with 20 μg / m L for 24 h]. The intestinal permeability,levels of blood endotoxin and D-lactic acid（ D-Lac）,intestinal morphology and animal survival time and survival rates were observed. Results Compared with normal control group,the levels of intestinal permeability,D-Lac and endotoxin were significantly increased in sepsis rats（ P〈0. 01）. The pathological observation showed that the intestinal villi were obviously decreased,the inflammatory cells and red blood cells were significantly increased. In 3 d after conventional treatment,the intestinal barrier function were slightly improved,the levels of blood D-Lac and endotoxin were slightly reduced,and the intestinal injury had some extent of alleviation. MSCs treatment was better than the CT treatment. What＇s more,poly（ I： C） pre-stimulation significantly enhanced the protective effect of MSCs along on intestinal barrier function.The concentrations of blood D-Lac and endotoxin were significantly reduced in poly（ I： C） pre-stimulated MSCs group than in MSCs group（ P〈0. 05）. The intestinal glands and villi were obviously increased and the inflammatory cells were significantly decreased in this group. Conclusion Poly（ I： C） pre-stimulation enhances the protective effects of MSCs on intestinal barrier function in sepsis rats.